Predictive HCV Index Could Spare Biopsy for a Third of Fibrotic Patients

TOTTORI, Japan, Feb. 2 -- A third of patients with hepatitis C infections and hepatic fibrosis could be spared liver biopsies by the use of a new index that predicts significant fibrosis with three blood tests, according to researchers here.

The tool, called the FibroIndex, could also be used to monitor the success of antifibrotic therapy, wrote Masahiko Koda, M.D. of Tottori University here, and colleagues, in the Feb. issue of Hepatology.

The FibroIndex, which combines aspartate aminotransferase (AST), platelet counts, and gamma globulin measurements, was superior to two other predictive tools for predicting significant fibrosis, and allowed 35% of patients to avoid liver biopsy, the researchers reported. The other tests were the Forns index and the aminotransferase-to-platelet ratio index.

"Information on the stage of fibrosis in chronic hepatitis C is essential for making a prognosis and deciding on antiviral treatment," the Japanese team wrote. "Liver biopsy is the gold standard for fibrosis staging in chronic hepatitis. However, liver biopsy is invasive and costly and requires an experienced hepatologist."

Between 0.6% and 5% of patients who have undergone liver biopsy have had complications including death," the group added. "Moreover, recent studies have reported that inadequate sample size and sampling error frequently lead to underestimation of fibrosis stage and a high rate of inter- and intra-observer discrepancies."

To see whether they could develop a more accurate predictive model for fibrosis in patients with HCV infections, the authors collected clinical data on 402 consecutive patients with chronic HCV at the time of liver biopsy, including blood samples taken no more than three days before the biopsies.

Patients were excluded if they had HIV or hepatitis B co-infection, drank more than 10 g of alcohol per day, had other liver disease, previous interferon therapy, or clinical evidence of cirrhosis, such as gastroesophageal varices, ascites, or hepatic encephalopathy.

The investigators used multivariate logistic regression analysis to identify independent risk factors for fibrosis in 240 patients (estimation set), and found that three met criteria fit the bill.

"We constructed the FibroIndex as a simple score system: FibroIndex = 1.738 - 0.064 (platelets [x 10⁴/mm³]) + 0.005(AST [IU/L]) + 0.463 (gamma globulin [g/dl])," the authors wrote.

They then tested the index in two validation sets: 120 patients with fibrosis stages F0-F3, and the same set plus 42 more patients with F4 fibrosis.

The investigators found that the areas under the receiver operating characteristic curves of the FibroIndex for predicting significant fibrosis were 0.83 and 0.82 for the validation set. The predictive value of the FibroIndex was better than either the Forns index or the aminotransferase-to- platelet ratio index.

Using the best cutoff values for identifying the presence or absence of significant fibrosis, the authors found that 35% of the patients (101) could have been spared a liver biopsy had the FibroIndex been used.

They also found that when they applied the FibroIndex data to a subgroup of 30 patients who were subsequently treated with interferon and underwent a second biopsy more than a year after treatment, changes in the index values correlated with changes in fibrosis. In contrast, neither the aminotransferase-to-platelet ratio index nor Forns index correlated with fibrotic changes.

The FibroIndex was also a reliable predictor in patients with normal levels of alanine aminotransferase (ALT), a third of whom had significant fibrosis.

The authors noted that none of the three indices they compared could accurately predict fibrosis during interferon therapy, because of that drug's known platelet-depletion effects. But the indices could be used after the completion of therapy as surrogate markers for antifibrotic effects, they added.

"Because testing for AST, platelet count, and gamma globulin is routine in most hospitals and laboratories, their measurements are reliable and sufficiently accurate. Therefore, the FibroIndex would be available to any laboratory," the authors wrote.